Mixed germ cell sex cord-stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases.

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord-stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical "square off" quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff (PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to that seen in the germ cells of spermatocytic seminomas. Immunohistochemically, the germ cells of MGSCTs in one case reacted positively with antibody to AE1-AE3 by paranuclear dot-like or rodlike positivity. All three testicular MGSCTs had a negative reaction with the rest of antibodies, including placental alkaline phosphatase (PLAP), OCT4, and c-kit protein. Ovarian MGSCT in our series differed from the testicular lesions in both the germ cell component and the sex cord component. The germ cells in all four ovarian cases had cytomorphological and immunohistochemical features identical to those in classical seminomas/dysgerminomas. They possessed the typical "square off" quality of the nuclei, which were much more blastic, with more mitoses compared with the testicular tumors in our series, and they were PLAP (4/4), OCT4 (4/4) and c-kit protein (3/4) positive immunohistochemically. The cytoplasm of the germ cells in ovarian neoplasms contained PAS positive glycogen. Germ cells in one ovarian MGSCTs showed amplification of 12p. All other germ cells were negative for amplification of 12p. All five successfully analyzed cases showed no mutation in all studied exons and exon-intron junctions in c-kit and PDFGRA genes.